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Published on: May 15, 2021
Toll-like Receptor Agonist CBLB502 Protects Against Cisplatin-induced Liver and Kidney Damage in Mice
Pengzhen Niu1, Wenyu Zhao1, Qiong Wang2,3
1National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, P.R. China.
Background/Aim:
CBLB502, a Toll-like receptor-5 agonist derived from Salmonella flagellin, exerts protective roles against irradiation and chemical drugs in mammalian tissues and stimulates tissue regeneration. This study aimed to investigate whether CBLB502 can protect against liver and kidney damage induced by the chemotherapeutic drug cisplatin (CDDP) and the underlying mechanism of the protective effect.
Materials And Methods:
Mice were pretreated with CBLB502 [0.2 mg/kg, intraperitoneal (i.p.) injection] 0.5 h prior to administration of CDDP (20 mg/kg, i.p. injection), and analyses of the liver and kidney indices, blood biochemistry, and histopathology were performed.
Results:
Pretreatment with CBLB502 alleviated CDDP-induced liver and kidney damage. RNA sequencing and bioinformatic analysis indicated that CDDP induced a similar damage-promoting gene regulation pattern in the liver and kidney. CBLB502 protected against liver and kidney damage only after CDDP treatment primarily via different pathways. However, some CBLB502-regulated genes were common between the liver and kidney, including those involved in blood coagulation, fibrinolysis, hemostasis, apoptotic regulation, NF-kappaB signaling, and response to lipopolysaccharide, suggesting a general protective effect by CBLB502.
Conclusion:
Our data provide insights into the protective mechanism of CBLB502 against CDDP-induced tissue damage in the liver and kidney and might provide a basis for future studies on functional genes and regulatory mechanisms that mediate protection against chemoradiotherapy-induced damage.
Insights
CBLB502, a Toll-like receptor-5 agonist, protects against cisplatin-induced liver and kidney damage in mice. This study reveals its protective mechanisms, highlighting its potential against chemotherapy-induced tissue injury.
Area of Science:
- Pharmacology
- Toxicology
- Immunology
Background:
- CBLB502, a Toll-like receptor-5 agonist derived from Salmonella flagellin, demonstrates protective effects against irradiation and chemotherapy in mammalian tissues.
- It also possesses tissue regenerative properties.
Purpose of the Study:
- To investigate the protective potential of CBLB502 against liver and kidney damage induced by cisplatin (CDDP).
- To elucidate the underlying mechanisms of CBLB502's protective effect.
Main Methods:
- Mice were pretreated with CBLB502 (0.2 mg/kg, i.p.) 30 minutes before CDDP administration (20 mg/kg, i.p.).
- Liver and kidney indices, blood biochemistry, and histopathology were analyzed.
Main Results:
- CBLB502 pretreatment significantly alleviated CDDP-induced liver and kidney damage.
- RNA sequencing revealed distinct but overlapping pathways involved in CBLB502's protective effect in the liver and kidney, including those related to coagulation, apoptosis, and immune signaling.
- Commonly regulated genes suggest a general protective role of CBLB502.
Conclusions:
- CBLB502 exhibits protective effects against CDDP-induced liver and kidney damage.
- The study provides insights into the mechanisms of CBLB502's action, potentially informing future strategies against chemoradiotherapy-induced tissue damage.
